CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort

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• 作者：Vito Guarnieri (1)
  Claudia Battista (2)
  Lucia Anna Muscarella (1)
  Michele Bisceglia (3)
  Danilo de Martino (4)
  Filomena Baorda (1)
  Evaristo Maiello (5)
  Leonardo D’Agruma (1)
  Iacopo Chiodini (6)
  Celeste Clemente (3)
  Salvatore Minisola (7)
  Elisabetta Romagnoli (7)
  Sabrina Corbetta (6)
  Raffaella Viti (2)
  Cristina Eller-Vainicher (6)
  Anna Spada (6)
  Michela Iacobellis (10)
  Nazzarena Malavolta (11)
  Massimo Carella (1)
  Lucie Canaff (8) (9)
  Geoffrey N. Hendy (8) (9)
  David E. C. Cole (12)
  Alfredo Scillitani (2)
  
• 关键词：CDC73 ; HRPT2 ; Parafibromin ; Parathyroid tumours ; Atypical adenoma
• 刊名：Cellular Oncology
• 出版年：2012
• 出版时间：December 2012
• 年：2012
• 卷：35
• 期：6
• 页码：411-422
• 全文大小：816KB
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• 作者单位：Vito Guarnieri (1)
  Claudia Battista (2)
  Lucia Anna Muscarella (1)
  Michele Bisceglia (3)
  Danilo de Martino (4)
  Filomena Baorda (1)
  Evaristo Maiello (5)
  Leonardo D’Agruma (1)
  Iacopo Chiodini (6)
  Celeste Clemente (3)
  Salvatore Minisola (7)
  Elisabetta Romagnoli (7)
  Sabrina Corbetta (6)
  Raffaella Viti (2)
  Cristina Eller-Vainicher (6)
  Anna Spada (6)
  Michela Iacobellis (10)
  Nazzarena Malavolta (11)
  Massimo Carella (1)
  Lucie Canaff (8) (9)
  Geoffrey N. Hendy (8) (9)
  David E. C. Cole (12)
  Alfredo Scillitani (2)
  
  1. Genetics Unit, Ospedale “Casa Sollievo della Sofferenza- Istituto di Ricovero e Cura a Carattere Scientifico, 71013, San Giovanni Rotondo, Foggia, Italy
  2. Endocrinology Unit, Ospedale “Casa Sollievo della Sofferenza- Istituto di Ricovero e Cura a Carattere Scientifico, 71013, San Giovanni Rotondo, Foggia, Italy
  3. Pathology Unit, Ospedale “Casa Sollievo della Sofferenza- Istituto di Ricovero e Cura a Carattere Scientifico, 71013, San Giovanni Rotondo, Foggia, Italy
  4. Surgery Unit, Ospedale “Casa Sollievo della Sofferenza- Istituto di Ricovero e Cura a Carattere Scientifico, 71013, San Giovanni Rotondo, Foggia, Italy
  5. Oncology Unit, Ospedale “Casa Sollievo della Sofferenza- Istituto di Ricovero e Cura a Carattere Scientifico, 71013, San Giovanni Rotondo, Foggia, Italy
  6. Endocrinology and Diabetology Unit, Department of Medical Sciences, Fondazione Policlinico, Istituto di Ricovero e Cura a Carattere Scientifico, University of Milan, Milan, Italy
  7. Department of Clinical Sciences, University of Rome “Sapienza- Rome, Italy
  10. Pathology Unit, Ospedale “Miulli- 70021, Acquaviva delle Fonti, Bari, Italy
  11. Department of Internal Medicine, Policlinico S.Orsola Malpighi, Bologna, Italy
  8. Departments of Medicine, Physiology, and Human Genetics, McGill University, Montreal, Canada
  9. Calcium Research Laboratory, and Hormones and Cancer Research Unit, Royal Victoria Hospital, Montreal, Quebec, Canada, H3A 1A1
  12. Departments of Laboratory Medicine and Pathobiology, Medicine, and Genetics, University of Toronto, Toronto, Ontario, Canada, M5G 1L5
  

文摘

Objective To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort. Methods Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n--5), atypical adenoma (AA) (n--4) and typical adenoma (TA) (n--7), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations. IHC staining for parafibromin was performed and scored as positive if nuclear staining was at least partially IHC-positive. Results Mutations of CDC73 were observed in 9/15 (60?%) CA, 2/14 (14?%) AA, and 1/17 (6?%) TA tumors. A recurrent two basepair mutation in exon 7 -- c.679_680delAG -- accounted for half of all identified mutations. Absence of parafibromin nuclear staining was noted in 8/12 (67?%) CA, 2/13 (15?%) AA, and 3/17 (18?%) TA tumors. Median follow up times were 88?months for CA, 76?months for AA, and 104?months for TA patients. One patient, a member of a previously reported multiplex family with a germline CDC73 mutation was found to have a second adenoma after removal of an atypical adenoma. Conclusions Molecular screening and IHC are both useful tools in the differential diagnosis of parathyroid tumors, but both have limited sensitivity and specificity. CDC73 mutations and negative immunostaining were common in atypical adenomas, but no local recurrence was observed in any case with successful surgical removal after follow-up periods of 27 to 210?months.